In the European Union there were an estimated 36,900 new cases of thyroid cancer and 3600 deaths in 2012. Although thyroid cancer is rare, it is the most common endocrine cancer. Among thyroid tumors, the vast majority are differentiated carcinomas (approximately 90%), and medullary cancers make up between 5 and 10%.

Treatment for patients with early stage differentiated thyroid cancer is thyroidectomy, and radioiodine treatment is administered postoperatively to patients with persistent or recurrent disease. Patients with radioiodine refractory disease can be treated with cytotoxic chemotherapy, with limited benefit, or tyrosine kinase inhibitors. Unfortunately, the majority of these patients will progress.

Surgery is also the primary treatment for patients with medullary thyroid cancer. Postoperative radiation therapy may also be prescribed for patients who underwent incomplete resection or removal or have positive margins. Systemic therapy with traditional cytotoxic agents is an option for patients with progressive or metastatic disease.

There is a need for improved treatment for patients with thyroid cancer who have progressed on first line therapy. Prof. Martin Schlumberger of the Gustave Roussy in Villejuif, France, and coordinator of this study points out, “Nintedanib inhibits the vascular endothelial (VEGF), fibroblast (FGF), and platelet derived (PDGF) growth factor receptors. As such, we think that this targeted agent could stop further tumor growth and prevent related tumor escape mechanisms. Nintedanib could help patients who have progressed on compounds that block only one of these three growth factor receptors.”

EORTC trial 1209 will explore the safety and efficacy of nintedanib (BIBF1120) as second line therapy for patients with either differentiated or medullary thyroid cancer progressing after first line therapy. Patients enrolled in this phase II trial will be randomized in a two to one ratio in favor of the experimental arm.

This phase II trial plans to accrue a total of 143 patients who progress after the first line of treatment; 75 patients in the group with differentiated thyroid cancer, and 68 patients in the group with medullary thyroid cancer. Patients in the experimental arm will receive nintedanib and patients in the control arm will receive matching placebo. Patients will continue to receive treatment until disease progression (according to RECIST 1.1) is documented, toxicity is unacceptable, or the patient decides to cease treatment. The primary endpoint of this trial is progression-free survival. Upon disease progression treatment will be unblinded and patients in placebo arm will be offered the option of receiving nintedanib up to further progression.

EORTC trial 1209 will be conducted in 36 sites located in nine countries: Belgium, Denmark, France, Germany, Italy, Poland, Spain, The Netherlands, and the United Kingdom. This trial is coordinated by the EORTC Endocrine Tumors Task Force and supported by an Educational Grant from Boehringer Ingelheim.